Neutrophil Gelatinase-associated Lipocalin (NGAL) and Contrast Media Induced Nephropathy

Medical University of Graz

Status

Completed

Conditions

Contrast Media Induced Nephropathy (CIN)

Treatments

Other: oral fluid application

Other: application of intravenous volume

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01292317

Ek 21-278 ex 09/10 (Other Identifier)

CIN and NGAL 1.0

Details and patient eligibility

About

Introduction:

Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated Lipocalin (NGAL), a new biomarker predictive for acute renal injury has been shown to be capable for earlier diagnosis of acute contrast media induced nephropathy (CIN) in patients undergoing cardiac surgery.

Intravenous volume load is a widely accepted prophylaxis.

In this randomized and controlled study, only patients with the need for an intra-arterial contrast media (CM) application will be included and receive a standardized, weight-based, intravenous hydration before investigation.

It is the aim of this study:

to evaluate the magnitude of a risk for contrast media induced nephropathy (CIN) following intra-arterial angiography in a well defined group of high-risk patients.
to use urinary Neutrophil gelatinase-associated Lipocalin (NGAL) as an early predictor of contrast media induced nephropathy (CIN) after contrast media (CM) application.
to evaluate the clinical benefit of an early post-procedural i.v. hydration as compared to only pre-procedural volume expansion.

Patients with markedly increased urinary Neutrophil gelatinase-associated Lipocalin (NGAL) after investigation will be randomized into one of two study groups:

Patients of Group A will undergo standard treatment consisting of unrestricted oral fluid intake.

Patients of Group B will additionally receive 3-4 ml/kg BW/h 0.9 % saline intravenously for 6 hours.

Endpoints:

Primary endpoint: contrast media induced nephropathy (CIN) defined by an increase greater than 25% of baseline serum creatinine.

Secondary endpoint: NGAL, Cystatin C, and creatinine values, need for renal replacement therapy, death.

Full description

Introduction:

Over the last decades the growing demand for appropriate diagnosing and intervention in all fields of modern medicine has increased the necessity for use of iodinated contrast media (CM). Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN) and consecutively have a greater risk of death.

To date, a reliable laboratory value or test that recognizes acute renal damage before serum creatinine increases is still sought for. It would be a most helpful tool to initiate proper treatment on time. Neutrophil gelatinase-associated Lipocalin (NGAL), a new biomarker predictive for acute renal injury has been shown to be capable for earlier diagnosis of contrast media induced nephropathy (CIN) in patients undergoing cardiac surgery.

So far, an intravenous volume load is the only fairly proven and widely accepted prophylaxis. However, the optimal intravenous fluid regimen regarding the type, amount, route and duration of volume application has remained controversial. Habits of giving pre- and post-procedural volume have been widely differing throughout all randomized trials and, thus, are not comparable in the available studies. Unfortunately, most studies were also lacking statistical power, used different types of contrast media (CM) and definitions of contrast media induced nephropathy (CIN) or allowed for additional prophylactic measures, such as N-acetylcysteine or sodium bicarbonate in a varying percentage of their patients.

In our randomized and controlled study, only patients with the need for an intra-arterial contrast media (CM) application will be included. Patients scheduled for a diagnostic angiography and/or endovascular intervention will receive a standardized, weight-based, intravenous hydration before investigation. Only one type of contrast media (CM) and neither sodium bicarbonate, nor N-acetylcysteine is used throughout the study. The study will be performed according to the Consort-Statement 2010 for clinical trials.

It is the aim of our study:

to evaluate the magnitude of a risk for contrast media induced nephropathy (CIN) following intra-arterial angiography in a well defined group of high-risk patients.
to use urinary Neutrophil gelatinase-associated Lipocalin (NGAL) as an early predictor of contrast media induced nephropathy (CIN) after contrast media (CM) application.
to evaluate the clinical benefit of an early post-procedural i.v. hydration as compared to only pre-procedural volume expansion.

Patients with markedly increased Neutrophil gelatinase-associated Lipocalin (NGAL) values (criteria for randomization into one of two treatment groups see below) at 4 to 6 hours after investigation will be randomized into one of two study groups:

Patients of Group A will additionally receive 3-4 ml/kg BW/h 0.9 % saline intravenously for 6 hours.

Patients of Group B will undergo standard treatment consisting of unrestricted oral fluid intake, at least 500 ml tea or water provided by the ward, but no intravenous fluid application.

Criteria for Randomization (after 2nd NGAL testing):

Patients with NGAL levels > 150 ng/ml, if baseline was below 75 ng/ml.
Patients with doubling of NGAL values, if baseline was between 75 and 150 ng/ml.

Endpoints:

Primary endpoint: contrast media induced nephropathy (CIN) defined by an increase greater than 25% of baseline serum creatinine.

Secondary endpoint: NGAL, Cystatin C, and creatinine values, need for renal replacement therapy, death.

Enrollment

819 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with the need for intra-arterial angiography/angioplasty
Patients older than 18 years
Patients with clinically stable chronic renal insufficiency stage 2 and more (calculated GFR < 70 ml/min/1,73 m2)(65)
Written informed consent

Exclusion criteria

Pre-existing clinical and/or laboratory evidence of acute renal failure at the time of enrollment
Evidence of rhabdomyolysis
Patients on renal replacement therapy (34)
Patients with life-threatening underlying disease (sepsis, MOF, SIRS)
Contraindication for volume therapy
Pregnancy
Contrast media application within 7 days prior to intervention